Different peripheral expression patterns of the nicotinic acetylcholine receptor in dementia with Lewy bodies and Alzheimer's disease

BackgroundThe diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and peripheral immune cells points out their involvement in several pathological conditions. Indeed, the deregulated function of the nAChR was previously correlated with cognitive decline and neuropsychiatric symptoms in Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB).The evaluation in peripheral immune cells of nAChR subtypes, which could reflect their expression in brain regions, is a prominent investigation area.ObjectivesThis study aims to evaluate the expression levels of both the nAChR subunits and the main known inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with DLB and AD to better characterize their involvement in these two diseases.ResultsHigher gene expression levels of TNF alpha, IL6 and IL1 beta were observed in DLB and AD patients in comparison with healthy controls (HC). In our cohort, a reduction of nAChR alpha 4, nAChR beta 2 and nAChR beta 4 was detected in both DLB and AD with respect to HC. Considering nAChR gene expressions in DLB and AD, significant differences were observed for nAChR alpha 3, nAChR alpha 4, nAChR beta 2 and nAChR beta 4 between the two groups. Moreover, the acetylcholine esterase (AChE) gene expression was significantly higher in DLB than in AD. Correlation analysis points out the relation between different nAChR subtype expressions in DLB (nAChR beta 2 vs nAChR alpha 3; nAChR alpha 4 vs nAChR alpha 3) and AD (nAChR alpha 4 vs nAChR alpha 3; nAChR alpha 4 vs nAChR beta 4; nAChR alpha 7 vs nAChR alpha 3; nAChR alpha 7 vs nAChR alpha 4).ConclusionsDifferent gene expressions of both pro-inflammatory cytokines and nAChR subtypes may represent a peripheral link between inflammation and neurodegeneration. Inflammatory cytokines and different nAChRs should be valid and accurate peripheral markers for the clinical diagnosis of DLB and AD. However, although nAChRs show a great biological role in the regulation of inflammation, no significant correlation was detected between nAChR subtypes and the examined cytokines in our cohort of patients.

Automated summary

This study evaluated the expression levels of nAChR subunits and inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of DLB and AD patients. The results showed higher expression levels of TNF alpha, IL6, and IL1 beta in DLB and AD patients, and lower expression levels of nAChR alpha 4, nAChR beta 2, and nAChR beta 4 in DLB and AD patients. The findings suggest a peripheral link between inflammation and neurodegeneration.